The Impact of Microbiota-Immunity-Hormone Interactions on Autoimmune Diseases and Infection.

Autoimmune diseases are complex multifactorial disorders, and a mixture of genetic and environmental factors play a role in their onset. In recent years, the microbiota has gained attention as it helps to maintain host health and immune homeostasis and is a relevant player in the interaction between our body and the outside world. Alterations (dysbiosis) in its composition or function have been linked to different pathologies, including autoimmune diseases. Among the different microbiota functions, there is the activation/modulation of immune cells that can protect against infections. However, if dysbiosis occurs, it can compromise the host's ability to protect against pathogens, contributing to the development and progression of autoimmune diseases. In some cases, infections can trigger autoimmune diseases by several mechanisms, including the alteration of gut permeability and the activation of innate immune cells to produce pro-inflammatory cytokines that recruit autoreactive T and B cells. In this complex scenario, we cannot neglect critical hormones' roles in regulating immune responses. Different hormones, especially estrogens, have been shown to influence the development and progression of autoimmune diseases by modulating the activity and function of the immune system in different ways. In this review, we summarized the main mechanisms of connection between infections, microbiota, immunity, and hormones in autoimmune diseases' onset and progression given the influence of some infections and hormone levels on their pathogenesis. In detail, we focused on rheumatoid arthritis, multiple sclerosis, and systemic lupus erythematosus.

Microbiota Transplant and Gynecological Disorders: The Bridge between Present and Future Treatments.

Fecal microbiota transplantation (FMT) is a procedure that involves transferring fecal bacteria from a healthy donor to a patients' intestines to restore gut-immunity homeostasis. While FMT was primarily supposed to treat gastrointestinal disorders such as inflammatory bowel disease and irritable bowel syndrome-and especially Clostridium difficile infection (currently the only used as clinical treatment)-recent research has suggested that it may also become a potential treatment for gynecological disorders, including endometriosis and polycystic ovary syndrome (PCOS). On the contrary, vaginal microbiota transplantation (VMT) is a newer and less commonly used procedure than the FMT approach, and its potential applications are still being explored. It involves direct grafting of the entire vaginal microbiota of healthy women into the vaginal tract of patients to easily rebuild the local microbiota environment, restoring vaginal eubiosis and relieving symptoms. Like FMT, VMT is thought to have potential in treating different microbiota-related conditions. In fact, many gynecological disorders, such as bacterial vaginosis and vulvovaginal candidiasis, are thought to be caused by an imbalance in the vaginal microbiota. In this review, we will summarize the development, current challenges, and future perspectives of microbiota transplant, with the aim of exploring new strategies for its employment as a promising avenue for treating a broad range of gynecological diseases.

Effects of the learning curve on operative time and lymph node harvesting during robotic gastrectomy.

BACKGROUND: Gastric cancer is the fifth most frequent cancer globally. The introduction of minimally invasive surgery for gastric cancer aimed at reducing post-operative morbidity and hospital length of stay. Although the role of laparoscopic gastrectomy has been established, robotic gastric surgery has only recently gained popularity. The purpose of this study was to evaluate, with a multidimensional analysis, the learning curve of a single surgeon with extensive experience in laparoscopic gastrectomy. METHODS: We prospectively collected data from 104 gastric cancer patients who underwent surgery with a robotic approach from June 2015 to June 2019 by a single surgeon. We performed 21 total gastrectomies (TGs) and 83 subtotal gastrectomies (STGs). A D2 lymphadenectomy was performed in all the patients. Proximal and distal resection margins were tumoour-free in all patients. There were no intraoperative complications, and no conversions occurred. RESULTS: The plateau of the learning curve based on harvesting lymph nodes and operative time was not reached for TG. The learning curve of operative time for STG could be divided into three different phases: an early or learning phase from 1 to 27 cases, an intermediate or proficiency phase from 28 to 48 cases, and a late or mastery phase from 49 to 83 cases. The learning curve for harvesting lymph nodes was achieved after 41 cases in the STG group. CONCLUSION: This study shows that robotic gastrectomy is a complex procedure with a significant multiphasic learning curve. Nevertheless, the robotic learning curve seems to be more rapid than that of conventional laparoscopy. Most importantly, our results suggest that the robotic technique can provide oncological adequacy in terms of lymph node harvesting even in the very first phase of the learning curve.

Surgery for Sporadic Primary Hyperparathyroidism: Evolution over the Last Twenty Years in a Monocentric Setting.

The sporadic parathyroid pathology of surgical interest is primarily limited to lesions that are the cause of hormonal hyperfunction (primary hyperparathyroidism). In recent years, parathyroid surgery has evolved significantly, and numerous minimally invasive parathyroidectomy techniques have been developed. In this study, we describe a single-center and well-documented case series of sporadic primary hyperparathyroidism, surgically treated by a single operator in the Endocrine Surgery Unit of the Surgical Clinic of the University of Florence-Careggi University Hospital, recorded and updated in a dedicated database that embraces the entire evolutionary timeframe of parathyroid surgery. From January 2000 to May 2020, 504 patients with a clinical and instrumental diagnosis of hyperparathyroidism were included in the study. The patients were divided into two groups, based on the application of intraoperative parathyroid hormone (ioPTH). The analysis shows that the use of ioPTH with the rapid method could be ineffective in helping surgeons in primary operations, especially when ultrasound and scintiscan are concordant. The advantages obtained by not using intraoperative PTH are not only economic. In fact, our data shows shorter operating and general anesthesia times and hospital stays, having an important impact on patient biological commitment. Furthermore, the significant reduction in operating time makes it possible to almost triple the volume of activity in the same unit of time available, with an undeniable advantage for the reduction of waiting lists. In recent years, minimally invasive approaches have allowed surgeons to reach the best compromise between invasiveness and aesthetic results.

Duplication of the gallbladder in a patient with right colon cancer. A case report and review of the literature review.

AIM: Duplication of the gallbladder is a very rare congenital variant, showing an incidence of about 1 in 4000 in the population, occurring twice as often in women than in men. In the literature only a few cases of prenatal diagnosis are reported. The knowledge of the existence of this anatomical variable is very important in order to avoid complications and iatrogenic damage during interventional and surgical procedures involving the biliary tract or adjacent organs. CASE REPORT: A 79-year-old patient was admitted to our Hospital in May 2021 presenting abdominal pain. During hospitalization, a 5cm adenocarcinoma of the ascending colon was found. During surgery the known accessory gallbladder was found strongly adhering to the proximal transverse colon. The challenging viscerolysis maneuvers caused a lesion on one of the gallbladders, so we decided to proceed with cholecystectomy of both gallbladders. RESULTS AND DISCUSSION: Duplication of the gallbladder is a rare congenital anatomical variant and requires special attention to the biliary and arterial anatomy in order to avoid iatrogenic damage. This variant can complicate surgical treatment for complications that need urgent treatment, such as cholecystitis. Currently the technique of choice for the evaluation of the biliary tree is magnetic resonance cholangiography. Laparoscopic cholecystectomy is the treatment of choice. CONCLUSION: Surgeons should be aware of the different forms of presentation of gallbladder pathologies, also the ones that are not "the standard" of routine. Detailed preoperative study is essential to avoid a missed diagnosis. KEY WORDS: Gallbladder, Mininvasive surgery, Variant, Anatomical.

Multicenter retrospective cohort Italian study on elective laparoscopic cholecystectomy performed by the surgical residents.

PURPOSE: This retrospective multicenter cohort study aimed to evaluate the clinical outcomes (mortality rate, operative time, complications) of elective laparoscopic cholecystectomy (LC) when performed by a surgical resident in comparison to experienced consultant in the backdrop of Italian academic centers. METHODS: Retrospective review of all patients undergoing elective LC between January 2016 and January 2022 at six teaching hospitals across Italy was performed. Cases were identified using the Current Procedural Terminology (CPT) code 5123 (LC without cholangiogram). All cases of emergency surgery, ASA score > 3, or when cholecystectomy was performed with another surgical procedure, were excluded. All suitable cases were divided into 2 groups based on primary surgeon: consultant or senior resident. Main outcome was complication rates (intraoperative and peri/postoperative); secondary outcomes included operative time, the length of stay, and the rate of conversion to open. RESULTS: A total of 2331 cases (1425 females) were included, of which, consultants performed 1683 LCs (72%), while the residents performed 648 (28%) surgeries. The groups were statistically comparable regarding demographics, history of previous abdominal surgery, operative time, or intraoperative complications. The rate of conversion to open cholecystectomy was 1.42% for consultant and none for resident (p = 0.02). A statistically significant difference was observed between groups regarding the average length of stay (2.2 ± 3 vs 1.6 ± 1.3 days p = 0.03). Similarly, postoperative complications (1.7% vs 0.5%) resulted in statistically significant (p = 0.02) favoring resident group. CONCLUSIONS: Our study demonstrates that in selected patients, senior residents can safely perform LC when supervised by senior staff surgeons.

Fluorescent lymphography for thoracic duct identification: Initial experience of a simplified and feasible ICG administration.

INTRODUCTION: Indocyanine green (ICG) lymphography can be performed to obtain realtime fluorescent images of the thoracic duct (TD). The injection of ICG into the inguinal nodes usually is ultrasound-guided. Our hypothesis was to simplify the ICG administration until making it executable by unqualified personnel without ultrasound guidance. MATERIAL AND METHODS: From October 2019 to October 2021 we enroled 18 patients. ICG was injected with a 25 Gauge needle in the subcutaneous tissue of the inguinal region bilaterally 14-16 h before surgery. RESULTS: The TD was visualised in every case considered. The easy switching between fluorescence and white light visualization facilitated the identification and dissection of the TD avoiding involuntary injuries. CONCLUSIONS: The simplified ICG administration to identify TD during oesophagectomy is easy to perform, does not require specifically trained staff, is not time demanding and has comparable results to the procedure performed under ultrasound guide.

Non-conventional applications for transanal endoscopic microsurgery. A single center experience and a systematic review of literature.

INTRODUCTION: Transanal endoscopic microsurgery (TEM) and transanal endoscopic operation (TEO) have been initially described for local excision of rectal adenomas and selected cases of rectal carcinomas. In the past decade, however, several new indications raised, and others could raise in the future. The aim of this review was to evaluate, both in the literature and in our personal experience, the use of TEM and TEO for non-conventional applications, different from rectal tumors. EVIDENCE ACQUISITION: We conducted a systematic review of published papers and we selected articles reporting patients who underwent endoscopic surgery for other medical reason than polyp cancer resection, with TEM or TEO. PubMed, MEDLINE, EMBASE and bibliographies of the selected studies were searched for articles in English published up to May 2020 to identify all relevant articles. We excluded articles reporting TEM and TEO used for classical indications. We finally report our experience of non-conventional use of TEO in 5 patients with different diseases. EVIDENCE SYNTHESIS: The research revealed 800 papers and among them we selected 52 articles for a total of 697 patients. Of all patients, only 52 had intraoperative or postoperative complications, with only 10 patients requiring major surgery. CONCLUSIONS: Our study suggests that TEM and TEO may be valid alternatives to traditional surgery in situations other than its classical indication. These findings can positively impact on the care of patients, who could benefit from less invasive surgical procedures associated with lower morbidity.

Case Report: Management of Malignancy-Exacerbated Pemphigus Vulgaris During COVID-19 Pandemic.

Pemphigus vulgaris is an intraepidermal autoimmune mucocutaneous blistering disease whose etiopathogenesis includes various trigger factors, i.e., drugs and malignancies. We present a case of malignancy-exacerbated pemphigus vulgaris which required a careful diagnostic process in order to rule out paraneoplastic pemphigus, along with the challenges posed by the need of treating both cutaneous and oncologic diseases. Possible post-operative complications post-poned the start of first-line immunosuppressive treatment of pemphigus. Moreover, the infective risks had to be minimized during the peak of the COVID-19 pandemic in Italy. Intravenous immunoglobulins were chosen as "bridge" therapy before the tumor surgical excision, followed by rituximab in post-operative phase.

Enhanced Vasculogenic Capacity Induced by 5-Fluorouracil Chemoresistance in a Gastric Cancer Cell Line.

Chemotherapy is still widely used as a coadjutant in gastric cancer when surgery is not possible or in presence of metastasis. During tumor evolution, gatekeeper mutations provide a selective growth advantage to a subpopulation of cancer cells that become resistant to chemotherapy. When this phenomenon happens, patients experience tumor recurrence and treatment failure. Even if many chemoresistance mechanisms are known, such as expression of ATP-binding cassette (ABC) transporters, aldehyde dehydrogenase (ALDH1) activity and activation of peculiar intracellular signaling pathways, a common and universal marker for chemoresistant cancer cells has not been identified yet. In this study we subjected the gastric cancer cell line AGS to chronic exposure of 5-fluorouracil, cisplatin or paclitaxel, thus selecting cell subpopulations showing resistance to the different drugs. Such cells showed biological changes; among them, we observed that the acquired chemoresistance to 5-fluorouracil induced an endothelial-like phenotype and increased the capacity to form vessel-like structures. We identified the upregulation of thymidine phosphorylase (TYMP), which is one of the most commonly reported mutated genes leading to 5-fluorouracil resistance, as the cause of such enhanced vasculogenic ability.

Robotic gastric surgery: a monocentric case series and review of the literature.

INTRODUCTION: The technical complexity of D2 lymphadenectomy and esophago-jejunal anastomosis are the main factors that limit the application of laparoscopic surgery in the treatment of gastric cancer. Robotic assisted gastric surgery provides potential technical advantages over conventional laparoscopy but an improvement in clinical outcomes after robotic surgery has not been demonstrated yet. EVIDENCE ACQUISITION: Data from 128 consecutive patients who had undergone robotic gastrectomy for gastric cancer at our center institution from April 2017 to June 2020 where retrospectively reviewed from a prospectively updated database. A narrative review was then carried out on PubMed, Embase and Scopus using the following keywords: "gastric cancer," "robotic surgery," "robotic gastrectomy" and "robotic gastric surgery". EVIDENCE SYNTHESIS: Ninety-eight patients underwent robotic distal gastrectomy and 30 underwent robotic total gastrectomy. The mean value of estimated blood loss was 99.5 ml. No patients required conversion to laparoscopy or open surgery. The median number of retrieved lymph nodes was 42. No tumor involvement of the proximal or distal margin was found in any patient. The median time to first flatus and first oral feeding was on postoperative day 3 and 5, respectively. We registered 6 leakages (4.6%), namely, 1 duodenal stump leakage and 5 anastomotic leakages. No 30-day surgical related mortality was recorded. The median length of hospital stay was 10.5 days (range 4-37). CONCLUSIONS: Published data and our experience suggest that the robotic approach for gastric cancer is safe and feasible with potential advantages over conventional laparoscopy.

Laparoscopic diastasis recti abdominis and midline hernia repair.

BACKGROUND: Diastasis recti abdominis (DRA) is defined as an abnormally wide distance separates the two rectus muscles. Thinning and widening of the linea alba is an important risk factor for development midline hernia. In patient with DRA there is an increase rate of hernia recurrence. METHODS: We perform a retrospective study to assess the outcome of laparoscopic intraperitoneal hernia repair and linea alba plication combined with mesh placement to obtain an adequate overlap of midline hernia associated to an abdominal wall support. The inclusion criteria were patients who has a clinical diagnosis of primary midline hernias of any size with associated diastasis recti. The exclusion criteria were incisional hernias, hernias outside of the midline. A total of 12 patients fulfilled the inclusion criteria. No complication was observed over the follow-up period. The rates for recurrence were 0% over the follow-up period. RESULTS: Despite the limited data some assumptions can be drawn from this study. The presence of DRA and coexisting hernia involves a challenging choice of the surgical treatment. Whichever approach is taken, in order to achieve an effective correction, plication of the linea alba is required. The major goal of any abdominal wall repair is not only reduction of hernia sac and prevention of further herniation but also restoration of the integrity and restitution of abdominal wall functionality. CONCLUSIONS: A laparoscopic approach to midline hernias associated to DRA is feasible and reproducible. It is necessary future prospective studies on larger numbers to improve knowledge on the management of DRA.

Laparoscopic vaginal lateral suspension: technical aspects and initial experience.

BACKGROUND: Pelvic organ prolapse (POP) etiology is a combination of anatomical, physiological, genetic, lifestyle, and reproductive factors determine pelvic floor dysfunction. POP is very common across all ages women worldwide and has become an increasing socioeconomic problem with public health consequences, with symptoms that could lead to a significant decrease in quality of life. METHODS: This study retrospectively analyzes a small case series of our initial experience of laparoscopic vaginal suspension with mesh focusing on the technical aspects of the technique. Although sacrocolpopexy and sacrohysteropexy are the most performed surgical techniques, they are associated with serious complications. Laparoscopic vaginal suspension appears reproducible and safe to learn. RESULTS: Between November 2017 and January 2020, fifteen patients underwent laparoscopic vaginal suspension for pelvic organ prolapse repair. Despite the small number, for a minimally invasive skilled surgeon, we notice a significative reduction of the learning curve to become proficient in this procedure. CONCLUSIONS: The diagnosis and management of pelvic organ prolapse are further complicated by what is considered "successful" treatment. Laparoscopic vaginal suspension is a feasible surgical procedure for one-stage treatment of pelvic organ prolapse.

Emergency surgery for appendectomy and incidental diagnosis of superficial peritoneal endometriosis in fertile age women.

RESEARCH QUESTION: This study aimed to evaluate the presence of superficial peritoneal endometriosis (SUP) in women referred to emergency surgery for right iliac fossa (RIF) pain and undergoing an appendectomy, considering which factors may be useful to suspect and identify endometriosis. DESIGN: An observational case-control study was conducted on a group (n = 149) of fertile age women. After surgery, Group A was selected upon the diagnosis of endometriosis (n = 34); Group B (n = 115) represented the controls. Demographics, comorbidities and clinical findings were registered and analysed. RESULTS: Appendicitis of various grades of severity was diagnosed in all patients, but SUP was also identified in 23%, of which 14.7% also presented with endometriosis of the appendix. Women in Group A reported chronic pelvic pain, dysmenorrhoea, dyspareunia and oral contraceptive use more frequently. At multivariate analysis, factors associated with endometriosis were: age <40 years, autoimmune disorders, multiple allergies, abdominal chronic pain, associated gynaecological pain symptoms, Alvarado score ≤6, and inconclusive ultrasound findings. CONCLUSIONS: The incidental finding of SUP in fertile age women presenting with an acute RIF pain and undergoing emergency surgery is a relevant observation. Clinical history and symptoms should guide surgeons in performing a correct diagnosis and in referring the patient to the gynaecology specialist.

Salvage multivisceral abdominal surgery after caustic ingestion: Case report.

INTRODUCTION: Ingestion of caustic substances is a life-threatening medical emergency with high morbidity and mortality rate. CASE REPORT: We present a case report of young patient who presents to our department secondary to ingestion of caustic substances was submitted to multi-visceral resection surgery having saved his life after a long and complex multidisciplinary management. CONCLUSION: An aggressive surgical approach allows successful initial treatment of extended caustic injuries. Early surgical treatment is essential to improve the prognosis in these patients and refer the patient to large and experienced hospital represents the main goal to guarantee a surviving chance.

Comparison among different techniques for en-bloc resection of rectal lesions: transanal endoscopic surgery vs. endoscopic submucosal dissection vs. full-thickness resection device with Over-The-Scope Clip® System.

BACKGROUND: The aim of our retrospective study is to compare the efficacy and indications of transanal endoscopic microsurgery (TEM), endoscopic submucosal dissection (ESD), and endoscopic full-thickness resection device (FTRD) with Over-The-Scope Clip (OTSC®) System for en-bloc resection of rectal lesions. METHODS: This study collected 76 cases of rectal neoplasms from a single hospital institution. Primary endpoints were complete en-bloc resection, intraprocedural adverse events, R0 en-bloc resection and an early discharge of the patient. Secondary endpoints included procedure-related adverse events. RESULTS: Mean tumor sizes were statistically significant smaller among patients treated with FTRD rather than TEM and ESD. TEO and FTRD treated patients experienced a higher en-bloc resection rate, with a shorter procedure time and hospital stay. No significant difference concerning the R0 resection was found. TEO and FTRD recorded lower perforation rates as compared to ESD, whereas no difference emerged concerning the bleeding rate and the post-polypectomy syndrome rate. CONCLUSIONS: Our study showed that each technique has specific features, so that each one offers advantages and disadvantages. Nevertheless, all of them ensure high en-bloc resection rates, whereas no difference exists for R0 resection rate. TEO provides the possibility to remove low rectal large lesions as compared to ESD and FTRD.